Lipocalin 2 alleviates iron toxicity by facilitating hypoferremia of inflammation and limiting catalytic iron generation

Iron is an essential transition metal ion for virtually all aerobic organisms, yet its dysregulation (iron overload or anemia) is a harbinger of many pathologic conditions. Hence, iron homeostasis is tightly regulated to prevent the generation of catalytic iron (CI) which can damage cellular biomolecules. In this study, we investigated the role of iron-binding/trafficking innate immune protein, lipocalin 2 (Lcn2, aka siderocalin) on iron and CI homeostasis using Lcn2 knockout (KO) mice and their WT littermates. Administration of iron either systemically or via dietary intake strikingly upregulated Lcn2 in the serum, urine, feces, and liver of WT mice. However, similarly-treated Lcn2KO mice displayed elevated CI, augmented lipid peroxidation and other indices of organ damage markers, implicating that Lcn2 responses may be protective against iron-induced toxicity. Herein, we also show a negative association between serum Lcn2 and CI in the murine model of dextran sodium sulfate (DSS)-induced colitis. The inability of DSS-treated Lcn2KO mice to elicit hypoferremic response to acute colitis, implicates the involvement of Lcn2 in iron homeostasis during inflammation. Using bone marrow chimeras, we further show that Lcn2 derived from both immune and non-immune cells participates in CI regulation. Remarkably, exogenous rec-Lcn2 supplementation suppressed CI levels in Lcn2KO serum and urine. Collectively, our results suggest that Lcn2 may facilitate hypoferremia, suppress CI generation and prevent iron-mediated adverse effects.     

Immunology of histoplasmosis: Humoral and cellular activity from a polysacchari-de-protein complex and its deproteinized fraction in experimentally immunized mice

In a previous publication it was reported that a polysaccharide-protein complex (PPC), sensitive to -glucosidase, was isolated from Histoplasma capsulatum. This complex was strongly reactive in an agar gel diffusion assay with sera from patients with histoplasmosis, but was unreactive with sera from patients with coccidioidomycosis. Here, the studies with human sera have been expanded and attempts were made to determine the response of mice immunized with nonviable H. capsulatum or Cocccidioides immitis to PPC or its deproteinized fraction (D-PPC) using more sensitive tests for antibody and including also test for cell-mediated immunity. Histoplasmin and coccidioidin were compared with PPC or its deproteinized fraction (D-PPC) in all assays. In a counterimmunoelectrophoresis (CIE) assay, PPC and D-PPC reacted only with sera from patients with histoplasmosis, whereas cross reactions were noted with histoplasmin and coccidioidin using heterologous sera. Cross-reaction were observed with all four antigen preparations and both types of antisera using a micro complement fixation assay. The assay for macrophage migration inhibitory factor (MIF) was also relatively nonspecific, in that inhibition occurred with cells from animals sensitized with Histoplasma or Coccidioides using both homologous and heterologous antigens. In the footpad assay, histoplasmin and coccidioidin were highly cross-reactive in animals sensitized with the heterologous fungus, but the PPC and D-PPC from H. capsulatum elicited significant reactions only in animals sensitized with Histoplasma.     

The primary structure of rat ribosomal protein L38.

The amino acid sequence of the rat 60S ribosomal protein L38 was deduced from the sequence of nucleotides in three recombinant cDNAs. Ribosomal protein L38 has 69 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular weight of 8,081. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 11-13 copies of the L38 gene. The mRNA for the protein is about 450 nucleotides in length.     

The primary structure of rat ribosomal protein L12

The covalent structure of the rat 60S subunit protein L12 which is a component of the ribosomal elongation factor binding domain was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2-terminal amino acid sequence of the protein. L12 has 165 amino acids and a molecular weight of 17,834. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 11-13 copies of the L12 gene. The mRNA for the protein is about 800 nucleotides in length. Rat L12 is homologous to Saccharomyces cerevisiae L15. The cDNA contains the highly repetitive DNA sequence, R.dre.1, in the 3' noncoding region.     

On population abundance and niche structure

Recent published evidence indicates a negative correlation between density of populations and the distance of their environments to a suitably defined ‘niche centroid’. This empirical observation lacks theoretical grounds. We provide a theoretical underpinning for the empirical relationship between population density and position in niche space, and use this framework to understand the circumstances under which the relationship will fail. We propose a metapopulation model for the area of distribution, as a system of ordinary differential equations coupled with a dispersal kernel. We present an analytical approximation to the solution of the system as well as R code to solve the full model numerically. We use this tool to analyze various scenarios and assumptions. General and realistic demographic assumptions imply a good correlation between position in niche space and population abundance. Factors that modify this correlation are: transitory states, a heterogeneous spatial structure of suitability, and Allee effects. We also explain why the raw output of the niche modeling algorithm MaxEnt is not a good predictor of environmental suitability. Our results elucidate the empirical results for spatial patterns of population size in niche terms, and provide a theoretical basis for a structured theory of the niche.     

The Role of Community and Individuals in the Formation of Social Capital

Because social capital shapes many desirable socioeconomic outcomes, we ask what incentives drive private investments in social capital. We estimate the association between private investments in social capital (outcome variable) and the following explanatory variables: (a) individual-level variables from an optimal investment model, (b) spillovers from group social capital, (c) village income inequality, and (d) market openness. We draw on information from Tsimane’, a native Amazonian society of foragers and farmers in Bolivia, and equate social capital with gifts, help given, and communal labor offered by the household. Age bore an inverted U-shaped and income bore a positive association with social capital, but geographic mobility, wealth, and schooling bore no significant association with social capital. We found strong group-level associations even after instrumenting social capital; the association probably stems from strong kinship ties which tend to blur the line between the group and the individual. Village measures of social capital were positively and significantly associated with private investments in social capital. We found some evidence that village income inequality and market openness were negatively associated with private investments in social capital.     

Habitat fragmentation reduces plant progeny quality: a global synthesis

Most of the world's land surface is currently under human use and natural habitats remain as fragmented samples of the original landscapes. Measuring the quality of plant progeny sired in these pervasive environments represents a fundamental endeavour for predicting the evolutionary potential of plant populations remaining in fragmented habitats and thus their ability to adapt to changing environments. By means of hierarchical and phylogenetically independent meta‐analyses we reviewed habitat fragmentation effects on the genetic and biological characteristics of progenies across 179 plant species. Progeny sired in fragmented habitats showed overall genetic erosion in contrast with progeny sired in continuous habitats, with the exception of plants pollinated by vertebrates. Similarly, plant progeny in fragmented habitats showed reduced germination, survival and growth. Habitat fragmentation had stronger negative effects on the progeny vigour of outcrossing‐ than mixed‐mating plant species, except for vertebrate‐pollinated species. Finally, we observed that increased inbreeding coefficients due to fragmentation correlated negatively with progeny vigour. Our findings reveal a gloomy future for angiosperms remaining in fragmented habitats as fewer sired progeny of lower quality may decrease recruitment of plant populations, thereby increasing their probability of extinction.     

The primary structure of rat ribosomal protein S19

The covalent structure of rat ribosomal protein S19 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed from the NH2-terminal amino acid sequence of the protein. Ribosomal protein S19 contains 144 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular weight of 15,944. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 15-18 copies of the S19 gene. The mRNA for the protein is about 640 nucleotides in length. Rat S19 is related to Saccharomyces cerevisiae S16A and to Halobacterium marismortui S12.